CN111994434A

CN111994434A - Biological sample preservation method and biological sample preservation box

Info

Publication number: CN111994434A
Application number: CN202010867003.0A
Authority: CN
Inventors: 张小刚; 吴军剑; 莫英
Original assignee: Shanghai Danrui Biomedical Technology Co ltd
Current assignee: Shanghai Danrui Biomedical Technology Co ltd
Priority date: 2020-08-26
Filing date: 2020-08-26
Publication date: 2020-11-27

Abstract

The biological sample is placed in a container for preservation, a first heat exchange agent and a second heat exchange agent are arranged in the container, the pretreatment temperature of the first heat exchange agent is different from the preservation standard temperature range of the biological sample, and the pretreatment temperature of the second heat exchange agent is in the preservation standard temperature range of the biological sample; the first heat-exchange agent and the biological sample, and the first heat-exchange agent and the second heat-exchange agent are arranged at intervals, and the biological sample is contacted with the second heat-exchange agent. The biological sample storage container may serve as the container.

Description

Biological sample preservation method and biological sample preservation box

Technical Field

The application relates to the technical field of biological sample preservation, in particular to a biological sample preservation method and a biological sample preservation box.

Background

Many biological samples are very sensitive to temperature, and the preservation temperature directly affects the quality of the biological samples, so the biological samples need to be preserved and transported by adopting special means and devices. For example, the standard temperature for storing platelet samples and single-harvest leukocyte suspension samples is usually 10-25 ℃, the standard temperature for storing whole blood and erythrocyte blood (excluding frozen erythrocytes) samples is usually 2-8 ℃, so that the metabolism speed of cells is reduced as much as possible, and meanwhile, nutrients and enzymes for maintaining cell activities are not negatively influenced.

Currently, biological samples are mainly stored and transported through a refrigerator, as shown in fig. 1, a conventional refrigerator includes a box 101 and a cover 102, the top of the box 101 is open, the interior of the box 101 is a hollow structure for containing biological samples, and the cover 102 is used for closing the top of the box 101. The method for preserving and transporting the biological sample by adopting the conventional refrigerator comprises the following steps: freezing the ice row or the ice bag in an environment of not more than-20 ℃ to ensure that the temperature of the ice row or the ice bag is not more than-20 ℃; placing the frozen ice row or ice bag in a refrigerator; protecting and packaging the vessel or the sample bag containing the biological sample; placing the protectively packaged biological sample on a row or bag of ice in a freezer; the refrigerator loaded with the biological sample is sealed and then transported to the destination via cold chain logistics.

The above-mentioned conventional methods for storing and transporting biological samples have disadvantages: 1. the temperature in the refrigerating box in the storage and transportation process cannot be guaranteed to be within the storage temperature range of the biological sample, particularly for the biological sample with the storage standard temperature of 10-25 ℃, when the environmental temperature is not higher than 10 ℃, the temperature in the refrigerating box is lower than 10 ℃, so that the quality of the biological sample is influenced; 2. the vessel or sample bag containing the biological sample is not fixed in position in the refrigerator, is easy to slide in the transportation process, and has the risk of breakage due to collision even if the vessel or sample bag containing the biological sample is protected and packaged.

Disclosure of Invention

The application provides a biological sample preservation method and a biological sample preservation box, which aim to solve the problems that in the prior art, the temperature control of a biological sample is not ideal and the risk of transportation rupture is high in the preservation and transportation processes.

In a first aspect, the present application provides a biological sample preservation method, placing the biological sample in a container for preservation, wherein a first heat exchange agent and a second heat exchange agent are arranged in the container, a pretreatment temperature of the first heat exchange agent is different from a preservation standard temperature range of the biological sample, and a pretreatment temperature of the second heat exchange agent is within the preservation standard temperature range of the biological sample; the first heat-exchange agent and the biological sample, and the first heat-exchange agent and the second heat-exchange agent are arranged at intervals, and the biological sample is contacted with the second heat-exchange agent.

In some embodiments of the present application, at least one barrier is disposed between the first heat-exchange agent and the biological sample, and between the first heat-exchange agent and the second heat-exchange agent.

Further, the interlayer is made of a heat insulation material, and the heat insulation material is selected from at least one of polyurethane, polystyrene, phenolic foam and glass wool.

In some embodiments of the present application, when the preservation standard temperature of the biological sample is lower than the ambient temperature, the first heat-exchange agent is a coolant, and the pretreatment temperature of the first heat-exchange agent is lower than the preservation standard temperature of the biological sample.

In some embodiments of the present application, the standard temperature for preserving the biological sample is 2-8 ℃ and is lower than the ambient temperature, correspondingly, the first heat exchange agent is a coolant, the pretreatment temperature of the first heat exchange agent is less than or equal to-20 ℃, and the pretreatment temperature of the second heat exchange agent is 2-8 ℃.

In some embodiments of the present application, the standard temperature for preserving the biological sample is 10 to 25 ℃ and lower than the ambient temperature, and correspondingly, the first heat-exchange agent is a coolant, the pretreatment temperature of the first heat-exchange agent is 2 to 8 ℃, and the pretreatment temperature of the second heat-exchange agent is 20 to 25 ℃.

In some embodiments of the present application, when the standard temperature for preservation of the biological sample is higher than the ambient temperature, the first heat-exchange agent is a heat storage agent, and the pretreatment temperature of the first heat-exchange agent is higher than the standard temperature for preservation of the biological sample.

In some embodiments of the present application, the biological sample is at least one of blood, plasma, blood cells, serum, and platelets of a warm-blooded mammal ex vivo, or the biological sample is at least one of animal cells, plant cells, animal tissues, animal organs, and microorganisms.

In some embodiments of the present application, the biological sample is contained by at least one of a specimen bag, a specimen vial, a specimen tube, and a specimen cartridge.

In a second aspect, the present application provides a biological sample storage container, which can store and transport a plurality of biological samples by using the biological sample storage method described in the first aspect. The biological sample storage box comprises a box body, wherein at least one reagent containing groove and at least one sample containing groove are formed in the box body, and the reagent containing groove and the sample containing groove are arranged at intervals; the agent placing groove is used for placing a first heat exchange agent, and the pretreatment temperature of the first heat exchange agent is different from the preservation standard temperature range of the biological sample; the sample placing groove is used for placing a second heat exchange agent and a biological sample, and the pretreatment temperature of the second heat exchange agent is within the preservation standard temperature range of the biological sample.

The application provides a biological sample preservation method and biological sample preservation box, the method adopts first heat-exchange agent and second heat-exchange agent to preserve biological sample simultaneously, the preliminary treatment temperature of first heat-exchange agent with the second heat-exchange agent is different. Wherein the first heat-exchange agent is independently disposed in a container for holding a biological sample, i.e., is not in contact with either the second heat-exchange agent or the biological sample, and exchanges heat with air in the container, thereby bringing the ambient temperature inside the entire container within an appropriate temperature range to retard the rate of temperature change of the second heat-exchange agent and the biological sample. Further, the pretreatment temperature of the second heat-exchange agent is within the preservation standard temperature range of the biological sample, and the second heat-exchange agent is in contact with the biological sample so as to ensure that the temperature of the biological sample does not deviate from the preservation standard temperature range during preservation and transportation.

Under the environment temperature of 10 ℃ and 30 ℃, no matter the biological samples with higher low temperature requirement are stored and transported, such as whole blood and erythrocyte blood (excluding frozen erythrocyte) samples, or the biological samples with lower low temperature requirement are stored and transported, such as platelet samples and single-harvest leukocyte suspension samples, and the like, the method provided by the application ensures that the corresponding biological samples are in the standard temperature range of the storage in the storage and transportation process, thereby not causing negative influence on the quality of the biological samples. Especially, compared with the conventional storage and transportation method, the method provided by the application has obvious temperature control superiority at the ambient temperature of 10 ℃.

The biological sample storage box can be used as a container for storing biological samples, and when the biological samples are stored and transported, containers or sample bags containing the biological samples do not need to be additionally protected and packaged. In addition, the second heat exchange agent also has a fixing effect on the biological sample, thereby greatly reducing the risk of the biological sample being broken due to sliding collision.

Drawings

The technical solution and other advantages of the present application will become apparent from the detailed description of the embodiments of the present application with reference to the accompanying drawings.

Fig. 1 is a schematic view of a prior art refrigeration case.

FIG. 2 is a perspective view of the sample storage case of the first embodiment of the present application.

Fig. 3 is a top view of the housing of fig. 2.

FIG. 4 is a schematic view of the sample storage case for storing and transporting biological samples according to the first embodiment of the present application.

FIG. 5 is a diagram illustrating the effects of the sample storage case of the first embodiment of the present application on storing and transporting biological samples.

FIG. 6 is a first schematic view of the sample storage case with multiple sample wells according to the first embodiment of the present disclosure.

FIG. 7 is a second schematic view of the sample storage case with multiple sample wells according to the first embodiment of the present application.

FIG. 8 is a schematic view of the sample storage case according to the second embodiment of the present application.

Fig. 9 is a schematic view of the structure of the sample storage case according to the third embodiment of the present application.

Fig. 10 is a schematic view of the structure of the sample storage case according to the fourth embodiment of the present application.

FIG. 11 is a schematic flow chart of a method for storing and transporting a biological sample according to a fifth embodiment of the present application.

FIG. 12 is a schematic flow chart of a method for storing and transporting a biological sample according to a sixth embodiment of the present application.

Fig. 13 is a graph showing the trend of the change in the temperature in the refrigerator in 24 hours of storage and transportation in experimental example 1 and comparative example 1 of the present application, in which the solid line represents experimental example 1 and the dotted line represents comparative example 1.

Fig. 14 is a graph showing the trend of the change in the temperature in the refrigerator in 24 hours of storage and transportation in experimental example 2 and comparative example 2 of the present application, wherein the solid line represents experimental example 2 and the dotted line represents comparative example 2.

Fig. 15 is a graph showing the trend of the change in the temperature in the refrigerator in 24 hours of storage and transportation in experimental example 3 and comparative example 3 of the present application, in which the solid line represents experimental example 3 and the dotted line represents comparative example 3.

Fig. 16 is a graph showing the trend of the change in the temperature in the refrigerator in 24 hours of storage and transportation in experimental example 4 and comparative example 4 of the present application, in which the solid line represents experimental example 4 and the dotted line represents comparative example 4.

Detailed Description

The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. It is to be understood that the embodiments described are only a few embodiments of the present application and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.

In the description of the present application, it is to be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," and the like are used in the orientations and positional relationships indicated in the drawings for convenience in describing the present application and for simplicity in description, and are not intended to indicate or imply that the referenced devices or elements must have a particular orientation, be constructed in a particular orientation, and be operated in a particular manner, and are not to be construed as limiting the present application. Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, features defined as "first", "second", may explicitly or implicitly include one or more of the described features. In the description of the present application, "a plurality" means two or more unless specifically limited otherwise.

In the description of the present application, it is to be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; may be mechanically connected, may be electrically connected or may be in communication with each other; either directly or indirectly through intervening media, either internally or in any other relationship. The specific meaning of the above terms in the present application can be understood by those of ordinary skill in the art as appropriate.

In this application, unless expressly stated or limited otherwise, the first feature "on" or "under" the second feature may comprise the first and second features being in contact, or may comprise the first and second features not being in contact but being in contact with each other by way of additional features between them. Also, the first feature being "on," "above" and "over" the second feature includes the first feature being directly on and obliquely above the second feature, or merely indicating that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature includes the first feature being directly under and obliquely below the second feature, or simply meaning that the first feature is at a lesser elevation than the second feature.

The following disclosure provides many different embodiments or examples for implementing different features of the application. In order to simplify the disclosure of the present application, specific example components and arrangements are described below. Of course, they are merely examples and are not intended to limit the present application. Moreover, the present application may repeat reference numerals and/or letters in the various examples, such repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and/or configurations discussed. In addition, examples of various specific processes and materials are provided herein, but one of ordinary skill in the art may recognize applications of other processes and/or use of other materials.

The term "horizontal section" as used herein refers to a planar figure obtained by cutting a geometric body in a horizontal direction by a horizontal plane in a solid geometry.

The "standard temperature for preservation of a biological sample" as used herein refers to a preservation temperature at which the biological sample can maintain biological, chemical and physical properties required for the purpose of use of the biological sample. The biological sample is stored at a temperature such that at least a portion of the sample or a substantial portion of the sample remains viable, retains at least a portion of its biological function, and/or satisfies detection, application conditions after a storage period. For example: the standard storage temperature of the whole blood and erythrocyte blood (excluding frozen erythrocytes) samples is 2-8 ℃, and the standard storage temperature of the platelet samples and the single leukocyte suspension samples is 10-25 ℃.

In a first aspect, the present embodiments provide a method for preserving a biological sample, wherein the biological sample is at least one of blood, plasma, blood cells, serum, and platelets of a warm-blooded mammal ex vivo, or at least one of animal cells, plant cells, animal tissues, animal organs, and microorganisms. In one embodiment, the biological sample is an ex vivo biological sample.

The biological sample preservation method comprises the steps of placing the biological sample into a container for preservation, wherein a first heat exchange agent and a second heat exchange agent are arranged in the container, the pretreatment temperature of the first heat exchange agent is different from the preservation standard temperature range of the biological sample, and the pretreatment temperature of the second heat exchange agent is in the preservation standard temperature range of the biological sample; the first heat-exchange agent and the biological sample, and the first heat-exchange agent and the second heat-exchange agent are arranged at intervals, and the biological sample is contacted with the second heat-exchange agent.

Specifically, the container may be an object having a storage space, such as a box, a jar, a tank, or a box, and the material of the container may be a heat insulating material, such as at least one of polyurethane, polystyrene, phenolic foam, and glass wool. The first heat-exchange agent and the second heat-exchange agent may be a cold-storage agent or a heat-storage agent, the cold-storage agent may be at least one of an ice bag, an ice bank, an ice box, an ice pack, and an ice plate, for example, and the heat-storage agent may be a heat-storage agent product in the prior art.

In some embodiments of the present application, at least one barrier is disposed between the first heat-exchange agent and the biological sample, and between the first heat-exchange agent and the second heat-exchange agent. The first heat-exchange agent is isolated from the biological sample by a barrier layer, and the first heat-exchange agent is also isolated from the second heat-exchange agent, so as to avoid strong heat exchange phenomena between the first heat-exchange agent and the second heat-exchange agent. The material of the interlayer can also be a heat-insulating material, and the heat-insulating material is selected from at least one of polyurethane, polystyrene, phenolic foam and glass wool.

In some embodiments of the present application, when the preservation standard temperature of the biological sample is lower than the ambient temperature, the first heat-exchange agent is a coolant, and the pretreatment temperature of the first heat-exchange agent is lower than the preservation standard temperature of the biological sample. The pretreatment temperature of the second heat-exchange agent is within the preservation standard temperature range of the biological sample.

In some embodiments of the present application, when the standard temperature for preservation of the biological sample is higher than the ambient temperature, the first heat-exchange agent is a heat storage agent, and the pretreatment temperature of the first heat-exchange agent is higher than the standard temperature for preservation of the biological sample. The pretreatment temperature of the second heat-exchange agent is within the preservation standard temperature range of the biological sample.

Wherein the first heat-exchange agent is independently disposed in a container for holding a biological sample, i.e., is not in contact with either the second heat-exchange agent or the biological sample, and exchanges heat with air in the container, thereby bringing the ambient temperature inside the entire container within an appropriate temperature range to retard the rate of temperature change of the second heat-exchange agent and the biological sample. Further, the pretreatment temperature of the second heat-exchange agent is within the preservation standard temperature range of the biological sample, and the second heat-exchange agent is in contact with the biological sample. Under the dual action of the first heat-exchange agent and the second heat-exchange agent, the temperature of the biological sample is ensured not to deviate from the standard temperature range for storage during storage and transportation.

In a second aspect, embodiments of the present application provide a biological sample storage container, which can store a plurality of biological samples by using the biological sample storage method described in the first aspect, and can be used for transportation of the biological samples. The biological sample storage box can store and transport a single biological sample and can also store and transport a plurality of biological samples.

The preservation box mainly comprises a box body, the box body can be made of heat preservation materials, and preferably made of polyurethane. The inside of box has good spatial layout, is equipped with at least one and puts agent groove and at least one and puts a kind groove, put the agent groove with put kind groove interval and set up. The reagent placing groove is used for a first heat-exchange reagent, and the pretreatment temperature of the first heat-exchange reagent is different from the preservation standard temperature range of the biological sample. The sample placing groove is used for placing a second heat exchange agent and a biological sample, and the pretreatment temperature of the second heat exchange agent is within the preservation standard temperature range of the biological sample.

Furthermore, the sample placing grooves are multiple, and the multiple sample placing grooves are distributed around the sample placing grooves.

Further, a separation layer with a certain thickness is arranged between the reagent placing groove and the sample placing groove so as to avoid contact between the first heat-exchange agent and the biological sample and between the first heat-exchange agent and the second heat-exchange agent. This is because the first heat-exchange agent is different from the standard temperature range for preservation of the biological sample, and if the first heat-exchange agent is in contact with the biological sample and the first heat-exchange agent is in contact with the second heat-exchange agent, a strong heat-exchange phenomenon may be caused, so that the temperature of the biological sample deviates from the standard temperature range for preservation thereof, thereby adversely affecting the quality thereof.

Further, the storage box further comprises a box cover, and the box cover and the box body can be detachably connected or fixedly connected. For example, the case lid with be detachable joint between the box, be equipped with at least one protruding structure on the box, correspondingly, be equipped with on the case lid with the groove structure of protruding structure looks adaptation, through protruding structure with the joint between the groove structure is fixed realizes the case lid seals the box. For another example, the box cover and the box body are fixedly connected, and the box cover and the box body are of an integrated structure and are manufactured through an integrated forming process. For another example, the box cover is fixedly connected with the box body, and the box cover is hinged on the box body.

The horizontal cross section of the reagent-containing groove and the sample-containing groove may be any regular or irregular shape, such as a circle, an ellipse, a polygon, etc., and the polygon may be a rectangle, a square, a diamond, a hexagon, etc.

In the first embodiment of this application, as shown in fig. 2, the storage box includes a box 1 and a box cover 2, the box 1 and the box cover 2 are detachably connected, a protruding structure 3 is provided on the box 1, and a slot 4 adapted to the protruding structure is provided on the box cover 2.

The box body 1 is internally provided with two agent containing grooves 5 and a sample containing groove 6, the two agent containing grooves 5 correspond to a first agent containing groove 51 and a second agent containing groove 52, and the sample containing groove 6 is arranged between the first agent containing groove 51 and the second agent containing groove 52. The storage box is particularly suitable for storing and transporting single biological samples.

Further, the sample well 6 is located at the center of the inside of the box body 1, the first reagent well 51 is located at the left side of the sample well 6, and the second reagent well 52 is located at the right side of the sample well 6.

Further, as shown in fig. 3, the first sample well 51 and the second sample well 52 are each rectangular in horizontal cross section with a uniform shape and size, the sample well 6 is preferably hexagonal in horizontal cross section, and the long side L1 of the rectangle is adjacent to and parallel to the long side L2 of the hexagon.

When only a single biological sample is placed in the sample-placing chamber 6, a sample bag (for example, a blood bag) or a sample bottle is usually used to contain the biological sample, and when a sample bottle is used to contain the biological sample, the second heat-exchange agent has a slightly poor fixing effect on the sample bottle, that is, the sample bottle may slide in the sample-placing chamber 6 during transportation, and in order to avoid a problem of leakage of the sample bottle due to sliding collision, the horizontal cross section of the sample-placing chamber 6 is designed to be hexagonal. For the sample accommodating groove 6 with a hexagonal horizontal section, an a angle and a β angle are formed at the a end and the B end which are oppositely arranged, respectively, and the angles of the a angle and the β angle are equal and are both smaller than 180 °, so that after a sample bottle containing a biological sample is placed in the sample accommodating groove 6, the a end and the B end often have a vacant space because the sample bottle cannot be fully fitted with the a end and the B end; the empty space has a buffering function, and compared with a sample placing groove with the angle alpha and the angle beta of 180 degrees (namely, the horizontal cross section of the sample placing groove is quadrilateral, such as rectangle, square and the like), the empty space effectively reduces the stress area between the sample bottle and the inner side wall of the sample placing groove 6, so that the risk of liquid leakage of the sample bottle caused by sliding collision is reduced. In addition, if a sample bag (for example, a blood bag) is used to contain a biological sample, the second heat-exchange agent generally has a desirable fixing effect on the sample bag, and only the second heat-exchange agent with a specification matched with the size of the sample bag needs to be selected according to the size of the sample bag, so as to ensure that the sample bag does not slide in the sample-placing groove 6 during transportation.

Further, for the sample placing groove 6 with a hexagonal horizontal section, the straight distance between the end a and the end B is L3, the length of L1 is greater than the length of L3, and the groove depth of the first and second

agent placing grooves

52 and 52 is equal and not lower than the groove depth of the sample placing groove 6. The purpose of this design is: the volume of the agent containing groove is enlarged as much as possible, and the heat exchange area is enlarged to improve the heat exchange effect, thereby being beneficial to maintaining the internal environment temperature of the storage box.

Further, when the preservation box is used for transporting a biological sample 8, at least one first heat-exchange agent 7 is respectively placed in the first agent placing groove 51 and the second agent placing groove 52, and the first heat-exchange agent 7 is not contacted with the biological sample 8; a biological sample 8 and at least one second heat-exchange agent 9 are placed in the sample placing groove 6, and the biological sample 8 is in contact with the second heat-exchange agent 9.

For example: as shown in fig. 4 and 5, one first heat-exchange agent 7 is placed in each of the first agent placing tank 51 and the second agent placing tank 52, one biological sample 8 and two second heat-exchange agents 9 are placed in the sample placing tank 6, and the two second heat-exchange agents 9 are respectively located on both sides of the biological sample 8.

It should be noted that, when a plurality of samples need to be stored and transported, a plurality of sample holding grooves may be provided in the sample storage box according to the first embodiment, and one sample and at least one second heat-exchange agent may be placed in each sample holding groove during transportation.

For example, as shown in fig. 6, a plurality of sample wells 6 are arranged in the box 1 at intervals in a row, a spacing area is provided between adjacent sample wells 6, a reagent well 5 is provided at the spacing area, and two reagent wells 5 are provided on both sides of each sample well 6.

For another example, as shown in fig. 7, a plurality of sample wells 6 are arranged in a row in the box 1; the sample placing grooves 6 are internally provided with two reagent placing grooves 5 which are respectively arranged at two sides of the sample placing grooves 6.

Preferably, at least one partition board is arranged in the sample placing groove to divide at least two sample accommodating cavities; and at least one side of the clapboard is provided with a second heat-exchange agent accommodating cavity.

The partition plate and the box body can be of an integrated structure, namely, the partition plate and the box body are manufactured through an integrated forming process. Or, the baffle with the box is detachable fixed connection, if: detachable clamping and fixing, and the like. The baffle is used for separating a plurality of sample holding cavities. The material of the baffle is polyurethane, high density polyethylene, acrylic resin and the like. The second heat-exchange agent accommodating cavity is used for accommodating the second heat-exchange agent. It should be noted that the number of the partition plates is not specifically limited, and can be selected according to actual needs.

The baffle can be the baffle of horizontal setting or the baffle of vertical setting, the baffle of horizontal setting is on a parallel with put the tank bottom surface in kind groove, the baffle of vertical setting is perpendicular to put the tank bottom surface in kind groove. The horizontally arranged partition board can divide a plurality of the sample accommodating cavities which are vertically distributed in the sample accommodating groove, and the vertically arranged partition board can divide a plurality of the sample accommodating cavities which are horizontally distributed in the sample accommodating groove. In one embodiment, a horizontal partition and a vertical partition can be arranged in the sample placing groove simultaneously according to requirements.

At least one side part of the clapboard is fixed with the groove bottom or the groove wall of the sample placing groove, and the fixing can be an integrated structure or a detachable fixed connection structure.

In a second embodiment of the present application, an improvement is made over the first embodiment to facilitate the transport of multiple samples, except that: as shown in fig. 8, two partition plates 9 are arranged in the sample-placing groove 6, so as to divide three sample-accommodating cavities 11, wherein the partition plates 9 are perpendicular to the bottom surface of the sample-placing groove 6. The partition board 9 and the box body are of an integrated structure, and the partition board 9 is positioned in the center of the sample placing groove 6. The bottom of the partition board 9 is fixed on the bottom of the sample placing groove 6, and other side parts of the partition board 9 are not connected with the sample placing groove 6, so that a second heat-exchange agent accommodating cavity 10 is formed on two sides of the partition board 9 respectively. Therefore, when the biological sample is stored and transported, the second heat exchange agents are arranged on two sides of the biological sample, so that the two sides of the biological sample are in contact with the second heat exchange agents, and the biological sample storage device is suitable for transporting samples with lower storage temperature, such as biological samples with the storage standard temperature range of 2-8 ℃.

In a third embodiment of the present application, an improvement is made over the first embodiment to facilitate the transport of multiple samples, except that: as shown in fig. 9, a partition 9 is provided in the sample well 6 to separate two sample-receiving chambers 11, and the partition 9 is perpendicular to the bottom surface of the sample well 6. The partition board 9 and the box body are of an integrated structure. The bottom of the partition board 9 is fixed on the bottom of the sample placing groove 6, one side of the partition board 9 is fixed on one groove wall of the sample placing groove 6, and the other side of the partition board 9 is not connected with the sample placing groove 6, so that a second heat-exchange agent accommodating cavity 10 is formed on one side of the partition board 9. Therefore, when the biological sample is stored and transported, one side of the biological sample is in contact with the second heat-exchange agent, and the biological sample storage device is suitable for transporting samples with higher storage temperature, such as biological samples with the storage standard temperature range of 10-25 ℃.

Preferably, at least one sample rack for fixing a plurality of biological samples is arranged in the sample placing groove; and in the sample placing groove, at least one side of the sample rack is provided with a second heat-exchange agent accommodating cavity 10.

The sample rack is preferably clamped and fixed in the sample placing groove. But the sample frame joint is fixed in put the central authorities department of appearance groove correspondingly put in the appearance inslot, the both sides of sample frame are equipped with one respectively and are used for placing the second heat exchange agent holding chamber of second heat exchange agent. For another example, the sample holder may also be fixed to a wall of the sample storage slot in a clamping manner, and correspondingly, a second heat exchanger accommodating cavity for accommodating the second heat exchanger is disposed on only one side of the sample holder in the sample storage slot.

It should be noted that the sample rack and the sample holding tank are detachably and fixedly connected, so that the position of the sample rack in the sample holding tank can be flexibly adjusted, and the specific position of the sample rack in the sample holding tank can be automatically selected according to actual needs and the specification of the second heat-exchange agent. The sample holder may be a centrifuge tube holder or a sample tube holder.

In a fourth embodiment of the present application, an improvement is made over the first embodiment to facilitate the transport of multiple biological samples, except that: as shown in fig. 10, a sample holder 12 for holding a plurality of biological samples is provided in the sample well 6; and in the sample placing groove 6, two sides of the sample holder 12 are respectively provided with a second heat exchange agent accommodating cavity 10.

The sample holder 12 is a centrifuge tube holder, and a plurality of centrifuge tube slots are provided thereon, and correspondingly, a plurality of biological samples are respectively contained in a centrifuge tube. The specification of the centrifuge tube is not particularly limited, for example, the centrifuge tube may be 15mL, 30mL, 50mL, etc., and may be selected by itself according to actual needs, only by adapting the centrifuge tube to the centrifuge tube bayonet.

In a fifth embodiment of the present application, the storage case described in the first embodiment is used to store and transport a single biological sample. The biological sample is a whole blood and erythrocyte blood (excluding frozen erythrocytes) sample, the preservation standard temperature range is 2-8 ℃, a blood bag is adopted to contain the whole blood and erythrocyte blood (excluding frozen erythrocytes) sample, and the sample amount in a single blood bag is not more than 400 mL.

As shown in fig. 11, the method includes the steps of:

s1, providing two first heat-exchange agents and two second heat-exchange agents, wherein the temperature of the first heat-exchange agents is-20 ℃, and the temperature of the second heat-exchange agents is 2-8 ℃.

Specifically, the first heat-exchange agent and the second heat-exchange agent are both preferably ice bags, the two first heat-exchange agents are respectively defined as a first heat-exchange agent No. 1 and a first heat-exchange agent No. 2, and the two second heat-exchange agents are respectively defined as a second heat-exchange agent No. 1 and a second heat-exchange agent No. 2. And (2) placing the No. 1 first heat-exchange agent and the No. 2 first heat-exchange agent in an environment with the temperature of minus 20 ℃, and performing freezing treatment for at least 24 hours to ensure that the temperatures of the No. 1 first heat-exchange agent and the No. 2 first heat-exchange agent are both minus 20 ℃. And placing the No. 1 second heat exchange agent and the No. 2 second heat exchange agent in an environment with the temperature of 2-8 ℃, and carrying out pre-cooling treatment for at least 24 hours, so that the temperature of the No. 1 second heat exchange agent and the temperature of the No. 2 second heat exchange agent are both 2-8 ℃.

S2, placing the first heat-exchange agent in the agent placing groove.

Specifically, the No. 1 first heat exchange agent is placed in the first agent placing groove, and the No. 2 first heat exchange agent is placed in the second agent placing groove.

S3, placing the single biological sample into the sample placing groove.

Specifically, a single blood bag containing a sample of whole blood and red blood cell-like blood (excluding frozen red blood cells) is placed in the sample-placing tank.

S4, placing the second heat-exchange agent in the sample placing groove, and enabling the second heat-exchange agent to be in contact with the biological sample.

Specifically, the No. 1 second heat exchange agent and the No. 2 second heat exchange agent are respectively placed on two sides of the biological sample, and the No. 1 second heat exchange agent and the No. 2 second heat exchange agent not only have a cold insulation function on the biological sample, but also have an effect of fixing the position of the biological sample in the sample placement groove, so that the problems of sliding, collision and the like of the biological sample in the transportation process are effectively solved.

And S5, closing the storage box and then transporting to a destination.

In a fifth embodiment of the present application, the holding tank described in the first embodiment is used to transport a single biological sample. The biological sample is a platelet sample or an apheresis leukocyte suspension sample, the preservation standard temperature range is 10-25 ℃, a blood bag is adopted for containing the platelet sample or the apheresis leukocyte suspension sample, and the sample amount in the single blood bag is not more than 600 mL.

As shown in fig. 12, the method includes the steps of:

s10, providing two first heat-exchange agents and one second heat-exchange agent, wherein the temperature of the first heat-exchange agents is 2-8 ℃, and the temperature of the second heat-exchange agents is 20-25 ℃.

Specifically, the first heat-exchange agent and the second heat-exchange agent are both preferably ice bags, the two first heat-exchange agents are respectively defined as a number 3 first heat-exchange agent and a number 4 first heat-exchange agent, and the one second heat-exchange agent is defined as a number 3 second heat-exchange agent.

And placing the No. 3 first heat exchange agent and the No. 4 first heat exchange agent in an environment with the temperature of 2-8 ℃, and carrying out pre-cooling treatment for at least 8 hours, so that the temperature of the No. 3 first heat exchange agent and the temperature of the No. 4 first heat exchange agent are both 2-8 ℃. And placing the No. 3 second heat exchange agent in a normal temperature environment of 20-25 ℃ for at least 8 hours to ensure that the temperature of the No. 3 second heat exchange agent is 20-25 ℃.

S20, placing the first heat-exchange agent in the agent placing groove.

Specifically, the No. 3 first heat exchange agent is placed in the first agent placing groove, and the No. 4 first heat exchange agent is placed in the second agent placing groove.

S30, placing the single biological sample into the sample placing groove.

Specifically, a single blood bag containing a platelet sample or a single blood bag containing a single leukocyte suspension sample is placed in the sample placing groove.

S40, placing the second heat-exchange agent in the sample placing groove, and enabling the second heat-exchange agent to be in contact with the biological sample.

Specifically, the No. 3 second heat exchange agent is placed on one side of the single blood bag, and the No. 3 second heat exchange agent not only is beneficial to maintaining the preservation standard temperature range of 20-25 ℃, but also has the function of fixing the position of the biological sample in the sample placing groove, so that the problems of sliding, collision and the like of the biological sample in the transportation process are effectively solved.

And S50, closing the storage box and then transporting to a destination.

The method for preserving a biological sample provided in the examples of the present application is compared with the method for preserving a biological sample in the prior art.

Experimental example 1

In this example, a single sample of whole blood and red blood cell (excluding frozen red blood cells) was stored and transported by the method described in the fourth example, and the sample of whole blood and red blood cell (excluding frozen red blood cells) was packed in a blood bag, and the volume of the single sample of whole blood and red blood cell (excluding frozen red blood cells) was 400 mL. The experimental example was carried out at an ambient temperature of 30 ℃ and a transport time of 24 h. The temperature recorder is arranged in the storage box, so that the temperature change condition in the storage box in the whole transportation process is monitored in real time. The temperature recorder is arranged in the sample placing groove and is in contact with the single sample.

Specifically, the method comprises the following steps:

s1', providing a No. 1 first heat-exchange agent, a No. 2 first heat-exchange agent, a No. 1 second heat-exchange agent and a No. 2 second heat-exchange agent, placing the No. 1 first heat-exchange agent and the No. 2 first heat-exchange agent in an environment with the temperature of minus 20 ℃ for freezing treatment for 24h, and placing the No. 1 second heat-exchange agent and the No. 2 second heat-exchange agent in an environment with the temperature of 4 ℃ for precooling treatment for 24 h.

S2', placing the No. 1 first heat-exchange agent and the No. 2 first heat-exchange agent in the first agent placing groove and the second agent placing groove respectively.

S3', placing the single whole blood and erythrocyte blood (excluding frozen red blood cells) samples in the sample placing grooves.

S4', placing the No. 1 second heat-exchange agent and the No. 2 second heat-exchange agent on two sides of the single whole blood and erythrocyte blood (excluding frozen erythrocytes) sample respectively.

S5', closing the storage box, and transporting to the destination.

Specifically, the number 1 first heat-exchange agent, the number 2 first heat-exchange agent and the number 1 second heat-exchange agent are all ice bags with the specification of 32 ounces, and the number 2 second heat-exchange agent is an ice bag with the specification of 16 ounces.

Experimental example 2

The experimental example differs from experimental example 1 only in that: the experimental example was carried out at an ambient temperature of 10 ℃.

Experimental example 3

In this example, a single platelet sample was stored and transported by the method described in the fifth example, and the platelet sample was packed in a blood bag, and the volume of the single platelet sample was 600 mL. The experimental example was carried out at an ambient temperature of 30 ℃ and a transport time of 24 h. The temperature recorder is arranged in the storage box, so that the temperature change condition in the storage box in the whole transportation process is monitored in real time. The temperature recorder is arranged in the sample placing groove and is contacted with the single platelet sample.

Specifically, the method comprises the following steps:

s10', providing a No. 3 first heat exchange agent, a No. 4 first heat exchange agent and a No. 3 second heat exchange agent, placing the No. 3 first heat exchange agent and the No. 4 first heat exchange agent in a low-temperature environment of 4 ℃ for precooling treatment for 8h, and placing the No. 3 second heat exchange agent in a normal-temperature environment of 24 ℃ for 8 h.

S20', placing the No. 3 first heat-exchange agent and the No. 4 first heat-exchange agent in the first agent placing groove and the second agent placing groove respectively.

S30', placing the single platelet sample in the sample placement groove.

S40', placing the No. 3 second heat-exchange agent on one side of the single platelet sample.

S50', closing the storage box, and transporting to the destination.

Specifically, the number 3 first heat-exchange agent, the number 4 first heat-exchange agent and the number 3 second heat-exchange agent are all ice bags with a specification of 32 ounces.

Experimental example 4

The experimental example differs from experimental example 3 only in that: the experimental example was carried out at an ambient temperature of 10 ℃.

Comparative example 1

This comparative example is a comparative example of experimental example 1. In this comparative example, a single sample of whole blood and red blood cell-based blood (excluding frozen red blood cells) was stored and transported in a conventional refrigerator as shown in FIG. 1, and the whole blood and red blood cell-based blood (excluding frozen red blood cells) was packed in a blood bag, and the volume of the single sample of whole blood and red blood cell-based blood (excluding frozen red blood cells) was 400 mL. The comparative example was carried out at an ambient temperature of 30 ℃ and a transport time of 24 h. The temperature recorder is arranged in the refrigerating box and is in contact with the single sample, so that the temperature change condition in the refrigerating box in the whole transportation process is monitored in real time.

The storage and transportation method of the comparative example comprises the steps of: firstly, providing three ice bags with the specification of 32 ounces and one ice bag with the specification of 16 ounces, and freezing all four ice bags at-20 ℃ for 24 hours to enable the temperatures of the four ice bags to be consistent; then, the four frozen ice bags after freezing treatment are placed in the refrigerating box; then, carrying out protective packaging on the blood bag containing the single whole blood and the erythrocyte blood (excluding the frozen erythrocytes) sample; then, the single whole blood and erythrocyte type blood (excluding frozen red blood cells) samples which are protected and packaged are placed in the refrigerating box and are positioned on the four ice bags; finally, the cooler is closed and transported to the destination.

Comparative example 2

This comparative example is a comparative example of experimental example 2. The present comparative example differs from comparative example 1 only in that: this comparative example was carried out at an ambient temperature of 10 ℃.

Comparative example 3

This comparative example is a comparative example to experimental example 3. In this comparative example, a single platelet sample was stored and transported in a conventional refrigerator as shown in FIG. 1, and the platelet sample was packed in a blood bag, and the volume of the single platelet sample was 600 mL. The comparative example was carried out at an ambient temperature of 30 ℃ and a transport time of 24 h. The temperature recorder is arranged in the refrigerating box and is in contact with the single sample, so that the temperature change condition in the refrigerating box in the whole transportation process is monitored in real time.

The storage and transportation method of the comparative example comprises the steps of: firstly, providing three ice bags with the specification of 32 ounces, and pre-cooling all the three ice bags for 8 hours in an environment of 4 ℃ so as to enable the temperatures of the three ice bags to be consistent; then, placing the three ice bags subjected to pre-cooling treatment in the refrigerating box; then, carrying out protective packaging on the blood bag filled with the single platelet sample; then, the single platelet sample in the protective package is placed in the refrigerator and placed on the three ice bags; finally, the cooler is closed and transported to the destination.

Comparative example 4

This comparative example is a comparative example to Experimental example 4. The present comparative example differs from comparative example 3 only in that: this comparative example was carried out at an ambient temperature of 10 ℃.

It should be noted that the dimensions of the biological sample storage boxes in the respective experimental examples were consistent with those of the storage boxes in the respective comparative examples, wherein the dimensions of the storage boxes refer to the length, width and height of the storage boxes.

When the ambient temperature is 30 ℃, as shown in fig. 13, the methods of experimental example 1 and comparative example 1 can meet the storage standard temperature requirement (2-8 ℃) of whole blood and erythrocyte blood (excluding frozen erythrocytes) samples. However, when the ambient temperature is 10 ℃, as shown in fig. 14, the method of experimental example 2 can meet the storage standard temperature requirement (2-8 ℃) of whole blood and erythrocyte blood (excluding frozen erythrocytes) samples; in comparative example 2, the temperature in the refrigerator exceeded the standard temperature range of 2-8 ℃ after 9.7 hours of storage and transportation of the sample, i.e., the temperature in the refrigerator decreased gradually from 2 ℃ and decreased to 0.4 ℃ after 24 hours of storage and transportation of the sample, thereby negatively affecting the quality of the whole blood and red blood cell type blood (excluding frozen red blood cells) samples. Thus, compared with the conventional biological sample storage and transportation method, the method provided by the application has obvious advantages in storing and transporting the whole blood and erythrocyte blood (excluding frozen erythrocytes) samples under the condition that the ambient temperature is 10 ℃.

When the ambient temperature is 30 ℃, as shown in fig. 15, the methods of experimental example 3 and comparative example 3 can both meet the requirement of the transportation and storage temperature of the platelet sample (10-25 ℃). However, when the ambient temperature is 10 ℃, as shown in fig. 16, the method of experimental example 4 can satisfy the requirement of the transportation and storage temperature of the platelet sample (10 to 25 ℃); in comparative example 4, the temperature in the refrigerator exceeded the transport storage temperature range of 10 to 25 ℃ after the sample was stored and transported for 10 hours, i.e., the temperature in the refrigerator gradually decreased from 10 ℃, and the temperature in the refrigerator decreased to 7 ℃ after the sample was stored and transported for 24 hours, thereby negatively affecting the quality of the platelet sample. Therefore, the method for storing and transporting the platelet sample has obvious superiority compared with the conventional biological sample storage and transportation method under the condition that the ambient temperature is 10 ℃.

In summary, in the environment temperature of 10 ℃ and 30 ℃, whether the biological samples with higher low temperature requirement, such as whole blood and erythrocyte blood (excluding frozen red blood cells) samples, or the biological samples with lower low temperature requirement, such as platelet samples, are transported, the method provided by the application ensures that the biological samples are in the standard temperature range for storage in the process of storage and transportation, so that the quality of the biological samples cannot be negatively influenced. And the conventional biological sample storage and transportation method has the defect of undesirable temperature control at a lower ambient temperature (such as 10 ℃).

In the above examples, experimental examples and comparative examples, the descriptions of the examples, experimental examples and comparative examples are focused on each other, and for parts which are not described in detail in a certain example, reference may be made to the description related to other examples.

The biological sample storage method and the biological sample storage box provided by the embodiment of the present application are described in detail above. The principle and the implementation of the present application are explained by applying specific examples, and the above description of the embodiments is only used to help understanding the technical solution and the core idea of the present application; those of ordinary skill in the art will understand that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; such modifications or substitutions do not depart from the spirit and scope of the present disclosure as defined by the appended claims.

Claims

1. A biological sample preservation method is characterized in that a biological sample is placed in a container for preservation, a first heat exchange agent and a second heat exchange agent are arranged in the container, the pretreatment temperature of the first heat exchange agent is different from the preservation standard temperature range of the biological sample, and the pretreatment temperature of the second heat exchange agent is in the preservation standard temperature range of the biological sample; the first heat-exchange agent and the biological sample, and the first heat-exchange agent and the second heat-exchange agent are arranged at intervals, and the biological sample is contacted with the second heat-exchange agent.

2. The method of claim 1, wherein at least one barrier is disposed between the first heat-exchange agent and the biological sample, and between the first heat-exchange agent and the second heat-exchange agent.

3. The method of claim 2, wherein the spacer is made of a thermal insulation material selected from at least one of polyurethane, polystyrene, phenolic foam, and glass wool.

4. A biological sample storage method according to any one of claims 1 to 3, wherein the first heat-exchange agent is a cold-storage agent when the storage standard temperature of the biological sample is lower than the ambient temperature, and the pretreatment temperature of the first heat-exchange agent is lower than the storage standard temperature of the biological sample.

5. The method according to claim 4, wherein the standard temperature for preserving the biological sample is 2 to 8 ℃ and lower than the ambient temperature, and the first heat-exchange agent is a coolant, the pretreatment temperature of the first heat-exchange agent is-20 ℃ or lower, and the pretreatment temperature of the second heat-exchange agent is 2 to 8 ℃.

6. The method according to claim 4, wherein the standard temperature for preserving the biological sample is 10 to 25 ℃ and lower than the ambient temperature, and the first heat-exchange agent is a coolant, the pretreatment temperature of the first heat-exchange agent is 2 to 8 ℃, and the pretreatment temperature of the second heat-exchange agent is 20 to 25 ℃.

7. The biological sample preservation method according to any one of claims 1 to 3, characterized in that when the preservation standard temperature of the biological sample is higher than the ambient temperature, the first heat-exchange agent is a heat storage agent, and the pretreatment temperature of the first heat-exchange agent is higher than the preservation standard temperature of the biological sample.

8. The method for preserving a biological sample according to claim 1, wherein the biological sample is at least one of blood, plasma, blood cells, serum, and platelets of a warm-blooded mammal ex vivo, or the biological sample is at least one of animal cells, plant cells, animal tissues, animal organs, and microorganisms.

9. The method of claim 1, wherein the biological sample is contained in at least one of a sample bag, a vial, a sample tube, and a cartridge.

10. A biological sample storage box is characterized by comprising a box body, wherein at least one reagent containing groove and at least one sample containing groove are arranged in the box body, and the reagent containing groove and the sample containing groove are arranged at intervals; the agent placing groove is used for placing a first heat exchange agent, and the pretreatment temperature of the first heat exchange agent is different from the preservation standard temperature range of the biological sample; the sample placing groove is used for placing a second heat exchange agent and a biological sample, and the pretreatment temperature of the second heat exchange agent is within the preservation standard temperature range of the biological sample.